Transforming growth factor-β and ciliary neurotrophic factor synergistically induce vasoactive intestinal peptide gene expression through the cooperation of Smad, STAT, and AP-1 sites

被引：29

作者：

Pitts, RL ^{[1
]}

Wang, SB ^{[1
]}

Jones, EA ^{[1
]}

Symes, AJ ^{[1
]}

机构：

[1] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2001年 / 276卷 / 23期

关键词：

D O I：

10.1074/jbc.M011759200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The cytokine ciliary neurotrophic factor (CNTF) and transforming growth factor-beta (TGF-beta) both induce transcription of the vasoactive intestinal peptide (VIP) gene through a 180-base pair cytokine response element (CyRE) in the VIP promoter. While CNTF induces STAT and AP-1 proteins to bind to cognate sites in the VIIP CS;RE, the mechanism through which TGF-beta acts to induce VIP gene transcription is not known. Here we show that Smad3 and Smad4 proteins can bind to two distinct sites within the VIP CyRE. These sites are absolutely required for the induction of VIP CyRE transcription, by TGF-beta. TGF-beta induces endogenous Smad;containing complexes to bind to these sites in human neuroblastoma cells. CNTF and TGF-beta synergize to induce VIP mRNA expression and transcription through the VIP CyRE. This synergy is dependent on the Smad, STAT, and AP-1 sites, suggesting that these two independent cytokine pathways synergize through the cooperation of pathway-specific transcription factors binding to distinct sites within the VIP CyRE.

引用

页码：19966 / 19973

页数：8

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